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自体骨髓浓缩物在绵羊骨关节炎模型中的应用:软骨和半月板修复的新视角

Autologous Bone Marrow Concentrate in a Sheep Model of Osteoarthritis: New Perspectives for Cartilage and Meniscus Repair.

作者信息

Desando Giovanna, Giavaresi Gianluca, Cavallo Carola, Bartolotti Isabella, Sartoni Federica, Nicoli Aldini Nicolò, Martini Lucia, Parrilli Annapaola, Mariani Erminia, Fini Milena, Grigolo Brunella

机构信息

1 Laboratory RAMSES, Rizzoli Orthopedic Institute , Bologna, Italy .

2 Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute , Bologna, Italy .

出版信息

Tissue Eng Part C Methods. 2016 Jun;22(6):608-19. doi: 10.1089/ten.TEC.2016.0033.

Abstract

INTRODUCTION

Cell-based therapies are becoming a valuable tool to treat osteoarthritis (OA). This study investigated and compared the regenerative potential of bone marrow concentrate (BMC) and mesenchymal stem cells (MSC), both engineered with Hyaff(®)-11 (HA) for OA treatment in a sheep model.

METHODS

OA was induced via unilateral medial meniscectomy. Bone marrow was aspirated from the iliac crest, followed by concentration processes or cell isolation and expansion to obtain BMC and MSC, respectively. Treatments consisted of autologous BMC and MSC seeded onto HA. The regenerative potential of bone, cartilage, menisci, and synovia was monitored using macroscopy, histology, immunohistochemistry, and micro-computed tomography at 12 weeks post-op. Data were analyzed using the general linear model with adjusted Sidak's multiple comparison and Spearman's tests.

RESULTS

BMC-HA treatment showed a greater repair ability in inhibiting OA progression compared to MSC-HA, leading to a reduction of inflammation in cartilage, meniscus, and synovium. Indeed, the decrease of inflammation positively contributed to counteract the progression of fibrotic and hypertrophic processes, known to be involved in tissue failure. Moreover, the treatment with BMC-HA showed the best results in allowing meniscus regeneration. Minor healing effects were noticed at bone level for both cell strategies; however, a downregulation of subchondral bone thickness (Cs.Th) was found in both cell treatments compared to the OA group in the femur.

CONCLUSION

The transplantation of BMC-HA provided the best effects in supporting regenerative processes in cartilage, meniscus, and synovium and at less extent in bone. On the whole, both MSC and BMC combined with HA reduced inflammation and contributed to switch off fibrotic and hypertrophic processes. The observed regenerative potential by BMC-HA on meniscus could open new perspectives, suggesting its use not only for OA care but also for the treatment of meniscal lesions, even if further analyses are necessary to confirm its healing potential at long-term follow-up.

摘要

引言

基于细胞的疗法正成为治疗骨关节炎(OA)的一种有价值的工具。本研究在绵羊模型中研究并比较了用Hyaff(®)-11(HA)工程化的骨髓浓缩物(BMC)和间充质干细胞(MSC)治疗OA的再生潜力。

方法

通过单侧内侧半月板切除术诱导OA。从髂嵴抽取骨髓,然后分别进行浓缩处理或细胞分离与扩增以获得BMC和MSC。治疗包括将自体BMC和MSC接种到HA上。术后12周,使用宏观检查、组织学、免疫组织化学和微型计算机断层扫描监测骨、软骨、半月板和滑膜的再生潜力。使用具有校正的Sidak多重比较和Spearman检验的一般线性模型分析数据。

结果

与MSC-HA相比,BMC-HA治疗在抑制OA进展方面显示出更大的修复能力,导致软骨、半月板和滑膜中的炎症减少。事实上,炎症的减少对抵消已知参与组织衰竭的纤维化和肥大过程进展有积极作用。此外,BMC-HA治疗在促进半月板再生方面显示出最佳效果。两种细胞策略在骨水平上均观察到较小的愈合效果;然而,与OA组相比,在股骨的两种细胞治疗中均发现软骨下骨厚度(Cs.Th)下调。

结论

BMC-HA移植在支持软骨、半月板和滑膜的再生过程中效果最佳,在骨方面效果稍差。总体而言,MSC和BMC与HA联合使用均能减轻炎症,并有助于抑制纤维化和肥大过程。BMC-HA在半月板上观察到的再生潜力可能开辟新前景,表明其不仅可用于OA护理,还可用于治疗半月板损伤,尽管需要进一步分析以确认其在长期随访中的愈合潜力。

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